[Genetic susceptibility to lung cancer].
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Genetic Predisposition to Disease↗
Biomedical subjects
J Jassem
Publications and source records attributed to J Jassem.
[Prognostic value of P53 protein in cells of non-small cell lung cancer].
The aim of the study was to evaluate the prognostic relevance of p53 protein in non-small cell lung cancer. The 95 surgically treated patients were included (53 patients with squamous cell carcinoma, 29--with adenocarcinoma, 5--with large cell carcinoma, and 8--with mixed type). The protein was assessed immunohistochemically with the use of monoclonal antibodies DO7, DAKO. Positive staining was present in 44 patients. There was no survival difference between groups with and without protein (median survival--36 and 33 months, respectively; p = 0.86). In the multivariate analysis the only characteristics with prognostic impact in the entire group was stage of the disease. There was no correlation between the expression of p53 protein and disease-free survival. These results indicate that there is no prognostic relevance of p53 protein in non-small cell lung cancer.
Adult↗
Sertoli cell tumor in androgen insensitivity syndrome--a case report.
A 26-year-old individual with androgen insensitivity syndrome was operated on for a 3200-g Sertoli cell tumor of the left gonad with retroperitoneal metastases. Six courses of bleomycin, etoposide, and cisplatin chemotherapy followed surgical treatment. Eighteen months after the initial surgery the patient is free of disease and in good health. The association of Sertoli cell tumor with androgen insensitivity syndrome is discussed and the relevant literature is briefly reviewed.
Adult↗
The occurrence of cerebellar hemangioblastoma in numerous first degree relatives with von Hippel-Lindau disease.
Von Hippel-Lindau disease is an autosomal dominant disorder caused by a mutation of VHL gene. The incidence of the disease is one in 36,000 and its clinical manifestation is a familial occurrence of hemangioblastoma of the central nervous system and retina, renal cell cancer and pheochromocytoma. Cerebellar hemangioblastoma is the most frequent or sometimes the only abnormality observed in this syndrome. We present a family with von Hippel-Lindau disease in which four first degree relatives had a cerebellar hemangioblastoma. This neoplasm caused the death of two brothers aged 27 and 24 years old, respectively and their mother aged 62. The third son of this family was affected ten years ago, at the age of 30. The healthy family members are counselled in Oncological Genetic Outpatient Unit in Gdańsk.
Adult↗
Clodronate in the management of bone metastases: a clinical study of 91 patients.
The aim of our study was to evaluate the efficacy of oral clodronate supplementing systemic therapy and/or palliative irradiation in 91 patients with painful bone metastases. Clodronate was administered at a daily dose of 1600-3200 mg for a median of 11 months (range 3--36 months). Partial or complete pain relief was achieved in 61 of 88 evaluable patients (69%). Response rate to clodronate in patients who additionally received palliative bone radiation was similar to that in patients who did not receive irradiation (68 and 71%, respectively). Eleven out of 12 bed-ridden patients with metastatic bone pain regained the ability of walking after the treatment with clodronate. Bone pain relief lasted from 1.5 to 36 months (mean 9.3 months). Clodronate was well tolerated in all but three cases (3%) in whom the treatment was discontinued due to intensive adverse gastrointestinal effects. In conclusion, we observed satisfactory symptomatic effect and low rate of adverse reactions in patients with metastatic bone lesions treated with oral clodronate. Further large controlled studies with thorough patient monitoring are warranted to evaluate the real benefit of clodronate, and to define its optimal scheduling.
Adult↗
Chemotherapy of advanced non-small cell lung cancer.
Until recently the role of chemotherapy in NSCLC has generally been questioned. Major concerns included marginal activity, considerable toxicity and high cost of this treatment. There has, however, been increasing evidence from individual studies and meta-analyses that chemotherapy in advanced NSCLC is able to increase survival and improve quality of life. In the past few years a series of active drugs (paclitaxel, docetaxel, gemcitabine, vinorelbine, topotecan and irinotecan) with novel mechanisms of action and favourable toxicity profiles have been developed. These agents appear to hold the promise of added therapeutic benefit. In consequence, chemotherapy has currently been considered an important part of the standard treatment in selected patients with advanced NSCLC. Despite recent developments, treatment outcomes in advanced NSCLC remain far from satisfactory, and new effective means are desperately needed if more patients are to enjoy the prospects of long-term survival.
Antineoplastic Agents↗
Late complications after postoperative radiotherapy in endometrial cancer: analysis of 317 consecutive cases with application of linear-quadratic model.
PURPOSE: To evaluate the incidence and risk factors for late complications after postoperative radiotherapy in endometrial cancer patients. METHODS AND MATERIAL: We performed a detailed retrospective analysis of 317 endometrial cancer patients given postoperative radiotherapy. A total of 247 patients (78%) received both intracavitary (BRT) and external beam irradiation (XRT); 49 patients (15%) received only BRT, and 21 (7%) only XRT. BRT included radium (Ra) and cesium (Cs). The mean dose rate for both isotopes at 0.5 cm from the applicator surface was 0.47 +/- 0.06 and 1.42 +/- 0.41 Gy/h, and the mean total dose was 50.5 +/- 10.3 and 48.4 +/- 15.0 Gy, respectively. Mean BRT dose at 0.5 cm was 50.1 +/- 11.7 Gy (range 14.5-71.0). Mean XRT dose in the International Commission on Radiation Units and Measurements (ICRU) reference point was 49.0 +/- 3.7 Gy (range 22.0-66.0) given in fractions of 1.54-2.49 Gy (mean 2.0 +/- 0.17) with a two- or four-field technique. Follow-up ranged from 4 to 21 years (median 7.3). Normalized total dose (NTD) including XRT and BRT doses was calculated based on a linear quadratic equation. RESULTS: Five-year overall survival rate was 75%, and 5-year disease-free survival (censored for noncancer deaths) was 81%. Late radiotherapy complications of any grade occurred in 158 patients (51%), including bowel complications in 41% and urinary bladder complications in 21%. A total of 37 grade 3 or 4 complications were observed in 33 patients (11%), of whom 32 were treated with both XRT and BRT. Severe bowel and/or urinary bladder complications occurred in 24 patients: in 14 of 72 patients (19.4%) who received XRT and Cs BRT, and in 10 of 172 patients (6.0%) applied XRT and Ra BRT. The higher proportion of severe bowel and/or bladder complications in the former group was due to the particularly frequent rate of these events (30.0%) in a subset of 47 patients who received XRT combined with Cs BRT at the dose rate of 1.7 Gy/h and the total BRT dose of 60 Gy. Higher NTD, XRT fraction dose, BRT dose rate, Cs BRT, two-field XRT technique, short overall radiotherapy time, and older age were correlated with increased late-event risk in univariate analysis. Multivariate Cox analysis demonstrated that the independent risk factors for late bowel complications were NTD (p = 0.000) and BRT dose rate (p = 0.036), whereas for bladder complications they were BRT dose rate (p = 0.005) and XRT fraction dose (p = 0.041). Neither clinical factor (age, parity, prior abdominal surgery, FIGO stage, diabetes mellitus, or hypertension) nor the surgery-to-radiotherapy interval, nor overall radiotherapy time was independently associated with the risk of late bladder or bowel complications. CONCLUSIONS: The risk of late complications after postoperative radiotherapy in endometrial cancer depends mainly on treatment-related factors: NTD, BRT dose rate, and XRT fraction dose. The use of combined XRT and BRT increases the risk of late effects. NTD calculations including BRT dose rate and XRT fraction dose enable estimation of radiobiologically equivalent dose and can decrease the risk of mistakes when the radiotherapy regimen is changed.
Actuarial Analysis↗
Does chemotherapy-induced leukopenia predict a response in small-cell lung cancer?
The correlation between chemotherapy-induced toxicity and treatment outcome in cancer patients has not been studied thoroughly. Our aim was to evaluate whether there is any relationship between chemotherapy-induced leukopenia and response to treatment in small-cell lung cancer (SCLC). Data derived from records of 228 patients treated within two prospective multicentre phase II studies were analysed. In the first study (101 patients) chemotherapy included vincristine, epirubicin and cyclophosphamide and, in the second (127 patients), cyclophosphamide, etoposide and epirubicin; both regimens were given every 3 weeks. In the present analysis, the correlation between treatment outcome (response rate and survival) and highest scores of leukopenia within the first two and up to the fourth chemotherapy cycle, respectively, was evaluated. The objective response rate for the entire group was 66%; 53% in patients whose white blood cells remained normal and 85% in those who developed leukopenia within the first two cycles (P = 0.000). In multifactorial analysis, also including other treatment- and patient-related factors, independent correlation with response to chemotherapy was found for leukopenia (P = 0.001), chemotherapy regimen (P = 0.002) and the combined relative dose intensity (P = 0.018), but not for patient sex, age, performance status, pre-study weight loss, extent of disease and initial white blood cell count. Leukopenia within the first two cycles of chemotherapy was not correlated with survival, whereas such correlation for leukopenia occurring up to the fourth cycle was at the borderline level (P = 0.06). These findings suggest a relationship between chemotherapy-induced leukopenia and tumour response in SCLC.
Adult↗
Gemcitabine in locally advanced and metastatic non-small cell lung cancer: the Central European phase II study.
The efficacy and toxicity profile of gemcitabine was evaluated in this phase II study of chemonaive patients with locally advanced and metastatic non-small cell lung cancer (NSCLC). Eighty patients (62 males, 18 females) were entered into this study. The disease stage was IIIA in ten patients, IIIB in 32, and IV in 38 patients. The median age was 61 (range 41 - 78). Karnofsky performance status was > or = 80 in 88% of patients. All patients were chemonaive, but five patients had received prior radiotherapy and 34 patients had undergone prior surgery. Gemcitabine 1250 mg/m2 was given as a 30-min intravenous infusion on days 1, 8, and 15 of a 28-day cycle. Patients received up to nine cycles (median three cycles). Of 872 doses 815 (93%) were administered without dose delay or modification. Of the 80 patients enrolled, 76 were evaluable for efficacy analysis, and 16 patients had a partial response for an overall response rate of 21.1% (95% CI, 11.9-30.3%). A further 47 patients (61.8%) had stable disease. Partial responses were seen in eight of 41 stage III patients (19.5%) and in eight of 35 stage IV patients (22.9%). The median time to progressive disease was 4.6 months. Median survival for all 80 patients was 7.1 months. Haematological toxicity was mild with grade 3 4 neutropenia in 6.3% of patients, grade 3 thrombocytopenia in 3.8% of patients, and grade 3 anaemia in 2.5% of patients. Grade 3 non-laboratory toxicity was: somnolence (1.3% of patients), infection (1.3%), nausea and vomiting (6.4%) and dyspnoea (5.1%). This study confirms that single-agent gemcitabine is active in advanced NSCLC and its well-tolerated safety profile makes it particularly suited to outpatient use.
Adenocarcinoma↗
Clinical implications of molecular abnormalities in lung cancer.
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Animals↗
Doxorubicin vs epirubicin, report of a second-line randomized phase II/III study in advanced breast cancer. EORTC Breast Cancer Cooperative Group.
The EORTC Breast Cancer Cooperative Group carried out a randomized trial to compare doxorubicin with epirubicin as second-line chemotherapy in patients with metastatic breast cancer. Two hundred and fifty-nine patients with at least one site of metastatic disease entered this trial, of whom 232 patients were eligible. Treatment consisted of doxorubicin 75 mg m(-2) or epirubicin 90 mg m(-2) i.v. every 3 weeks. The overall response rates for doxorubicin and epirubicin were 36% and 28% respectively (P = 0.173). The median time to progression was 23 weeks for doxorubicin and 19 weeks for epirubicin (P = 0.063) and the median duration of response was 40 weeks for doxorubicin and 32 weeks for epirubicin (P = 0.059). The median survival was 47 weeks for doxorubicin and 44 weeks for epirubicin (P = 0.196). Leucocyte count on retreatment day (P = 0.011) and platelet nadir (P = 0.031) were significantly lower in the doxorubicin-treated group. Also mucositis (P < 0.001), diarrhoea (P = 0.005) and haemorrhage (P = 0.048) were significantly worse in the doxorubicin arm. Nine patients on doxorubicin and two patients on epirubicin experienced congestive heart failure (CHF). At the dose levels used in this study, no statistical differences in response rate and survival were found between the two treatment arms. Treatment with doxorubicin tended to result in a slightly longer duration of response and time to progression but doxorubicin was more toxic than epirubicin.
Adult↗
[Platinum-based chemotherapy in renal transplant recipients with malignancies: a case report and review of literature].
Authors present a case of renal transplant recipient treated with a carboplatin-based chemotherapy for testicular embryonal carcinoma. The patient experienced severe treatment-related toxicity and died due to bone marrow aplasia 3 months after the diagnosis of cancer. The safety of platinum-based chemotherapy in renal transplant recipients is discussed with reference to the literature data.
Antineoplastic Agents↗
[Evaluation of the prognostic significance of P53 mutation in patients with non-small cell lung cancer].
Prognostic value of p53 gene mutation was determined in 95 radically operated non small cell lung cancer patients (78 males and 17 females, mean age 57.8 years). Study group included 62 cases of squamous cell carcinoma, 30--adenocarcinoma and 3--large cell carcinoma. There were 52 patients in stage I disease, 16--in stage II, 26--in stage IIIa and one--in stage IIIb. Paraffin-embedded samples of resected tumors were assayed for p53 mutations with the use of PCR/SSCP analysis. p53 mutation were present in 22 cases (23%). The median survival in patients with and without p53 mutations were 49 and 75 months (p = 0.46), respectively, and the five-year survival rate 53% and 50%, respectively. In stage I disease the median survival for patients with p53 mutation was 53 months and for those without mutations the median survival could not be determined as more then a half of them were alive. Median survival in stage II patients with and without mutations was 35 months and 44 months (p = 0.62), and in stage IIIA--9.5 months and 17 months, respectively (p = 0.37). The results of this study indicate that p53 gene mutation is not correlated with prognosis in non-small cell lung cancer patients.
Adult↗
TP53 mutational pattern in Spanish and Polish non-small cell lung cancer patients: null mutations are associated with poor prognosis.
Inactivation of TP53 tumor suppressor gene is the most frequent molecular alteration in NSCLC, involving up to 60% of cases. Furthermore, TP53 mutational spectrum is related to the type of mutagen exposure, as well as racial and/or diet differences. Nearly 95% of TP53 perturbations affect codons included within exons 5-8 which encode for almost the entire DNA-binding domain. In this study we addressed the possible prognostic value of the molecular alterations identified in exons 5-8 of the TP53 gene in DNAs from 151 paraffin-embedded NSCLC sections corresponding to 59 Spanish and 92 Polish stage I-IIIA resected patients. PCR/single-strand conformation polymorphism (SSCP) analysis revealed that the occurrence of TP53 exon 5-8 mutations was 17/59 (29%) in the Spanish cohort and 17/92 (18%) in the Polish group. However, when DNA sequencing analysis was performed, these frequencies were reduced because of the presence of SSCP-false positive, intronic and silent mutations and polymorphisms. Fifteen of the 59 Spanish NSCLC tumors (25%) harbored TP53 mutations affecting exons 5-8 coding sequences, whereas only 12 of 92 Polish neoplasms (13%) contained alterations in the central hydrophobic region of p53. Our results indicate that the occurrence of TP53 mutations affecting exon 5-8 coding sequences in some European NSCLC populations may be lower than previously reported, and that the TP53 mutational patterns of these cohorts differ somewhat. The Spanish NSCLC patients contained missense mutations (9/59, 15%) and a relatively high percentage of null mutations (5/59, 8%) while the Polish patients mostly harbored missense mutations (9/92, 10%) and only one tumor contained a null type (1/92, 1%). Moreover, most TP53 missense mutations in the Spanish group were located outside the conserved regions, whereas the same mutations in the Polish group affected conserved amino acids. Furthermore, the Polish patients harbored a high percentage of G-->A transitions (most of them at non-CpG sites), while G-->T transversions were predominant in the Spanish group. Our findings suggest that there may be different racial or exogenous factors in these two populations which may help to explain both the distinct TP53 mutational pattern and the lower frequency obtained in the Polish group. The presence of missense mutations did not confer a worse clinical outcome in these subsets of NSCLC patients. However, patients whose tumors contained null TP53 gene mutations had a 5 month median disease-free survival time in contrast with 42 months in those patients without mutations (P=0.008). These findings suggest that loss of p53 function may enhance tumor progression in NSCLC patients independently of whether dominant negative TP53 missense mutations are present.
Aged↗
Patient-related factors determining geometry of intracavitary applicators and pelvic dose distribution during cervical cancer brachytherapy.
PURPOSE: The aim of this study was to assess retrospectively the influence of the size of cervical cancer brachytherapy applicators (ovoids and uterine tandems) on pelvic dose distribution and to analyze the impact of various patient- and disease-related factors on applicators' geometry and on dose distribution in particular applications. METHODS AND MATERIALS: The subject of this study were 356 cervical cancer patients treated with Selectron LDR as a part of their radical radiotherapy. Analyzed factors included patient age, weight, number of vaginal deliveries, and disease stage. RESULTS: The use of larger vaginal applicators resulted in lower bladder and rectum doses and in higher point B doses (all p < 0.0001); longer uterine tandems produced lower rectum doses and higher point B doses (both p < 0.0001). Increasing patient age and disease stage resulted in a decreased frequency of use of large ovoids (both p < 0.0001) and of long tandems (age: p = 0.0069, stage: p = 0.004). As a result, higher doses to bladder (age: p < 0.0001, stage: p = 0.017) and rectum (age: p = 0.037, stage: p = 0.011) were observed. Increasing age also resulted in lower point B doses (p < 0.0001). Increasing patient weight correlated with less frequent use of long tandems (p = 0.0015) and with higher bladder doses (p = 0.04). Higher number of vaginal deliveries was related to the increase in the use of long tandems (p = 0.002); in patients who had had at least one vaginal delivery, point B doses were significantly higher (p = 0.0059). In multivariate analysis ovoid size and uterine tandem length were dependent on patient age (respectively: p < 0.001 and p = 0.001), disease stage (respectively: p = 0.003 and p = 0.008) and on the number of vaginal deliveries (respectively: p = 0.07 and p = 0.008). Doses to critical organs and to points B were dependent on patient age (respectively: p < 0.001, p = 0.011, and p < 0.001) and on disease stage (respectively: p < 0.001, p = 0.004, and p = 0.048). CONCLUSION: The results of this study allow for identification of some patient- and disease-related factors influencing pelvic dose distribution in cervical cancer brachytherapy. This potentially may enable optimization of the dose distribution in particular clinical situations.
Adult↗
Influence of brachytherapy applicators geometry on dose distribution in cervical cancer.
AIM: Although the relationship between the dose delivered to adjacent organs (urinary bladder and rectum) and the frequency and severity of treatment complications has been reported in many series, the factors influencing pelvic dose distribution are not well defined. The aim of the study was to assess retrospectively the influence of the size of cervical cancer brachytherapy applicators (ovoids and uterine tandems) on pelvic dose distribution and the impact of various therapy-dependent factors on patient anatomy and on dose distribution in particular applications. PATIENTS AND METHOD: The subject of this study were 356 cervical cancer patients treated with Selectron LDR as a part of their radical radiotherapy. Analysed factors included preceding external beam radiotherapy (EBRT) or brachytherapy applications, use of general anaesthesia for application and the system of pellet loading. RESULTS: Significant correlation was found between the size of applicators and doses to bladder, rectum and points B: larger vaginal applicators produced lower dose in bladder and rectum and higher dose in point B (all p < 0.0001), longer uterine tandems produced lower dose in rectum and higher dose in point B (both p < 0.0001). Significant decrease in the frequency of use of large applicators (ovoids: p < 0.0001, tandems: p = 0.055) and worsening of dose distribution, i.e. higher doses to critical organs (respectively: bladder p = 0.0012, rectum p = 0.02) and lower point B dose (p = 0.0001) were observed at consecutive brachytherapy applications. Similar situation occurred in patients, who received EBRT prior to brachytherapy (ovoids: p < 0.001, tandem: p = 0.04, bladder dose: p = 0.009, rectal dose: p = 0.073, point B dose: p = 0.059). Vaginal applicators were larger (p = 0.026) and the dose distribution was better (bladder: p = 0.023, rectum: p = 0.002, point B: p = 0.0001) in patients who had their insertions performed under general anaesthesia. The comparison of 2 consecutively used systems of pellet loading revealed more favourable dose distribution: lower dose for bladder (p = 0.014) and higher dose for point B (p < 0.0001) for the system, which utilised more sources in ovoids and in the distal part of the uterine tandem, in spite of more frequent use of smaller applicators in this group of patients. In multivariate analysis ovoid size was related to preceding external beam radiotherapy (p = 0.025). Uterine tandem length was dependent on the number of preceding intracavitary applications (p < 0.001) and preceding external beam radiotherapy (p = 0.007). Bladder dose was related to preceding brachytherapy (p = 0.011) and the pattern of pellet loading (p = 0.031). Rectal dose was dependent only on the use of general anaesthesia during application (p = 0.001) and point B dose was dependent on the pattern of pellet loading (p < 0.001) and marginally-on the use of preceding external beam radiotherapy (p = 0.06). CONCLUSIONS: The results of this study allow for identification of treatment-related factors determining pelvic dose distribution in cervical cancer brachytherapy and may potentially enable optimisation of this distribution in particular clinical situation.
Brachytherapy↗
Pretreatment minimal staging and prognostic factors for non-small cell lung cancer.
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Carcinoma, Non-Small-Cell Lung↗
A multicenter study of recombinant human erythropoietin (epoetin alpha) in the management of anemia in cancer patients receiving chemotherapy.
Current evidence suggests that epoetin alpha administration is well tolerated and effective in the management of anemia of cancer and cancer chemotherapy. An open-label, multinational, non-comparative study was conducted in 215 cancer patients with anemia secondary to chemotherapy with platinum- or non-platinum-based combinations. Epoetin alpha was administered s.c. (150 IU/kg three times/week) for a planned period of 16 weeks. The response rate of epoetin alpha, defined as an increase in hemoglobin level of 2 g/dl or more from baseline, was 67%. The rate of response was not related to the chemotherapy regimen administered (platinum or non-platinum based). The percentage of patients transfused and the transfusion rate during epoetin alpha treatment were reduced. Transfusional need was eliminated in 64 (75%) of the 85 patients transfused before the study start, after 1 month of therapy. Quality of life, assessed using a visual analog scale, improved markedly in patients who experienced a hematological response. These patients also experienced a statistically significant (p < 0.0001) improvement in mean WHO performance score. These findings indicate that epoetin alpha is a well tolerated and effective agent which increases hemoglobin concentration and reduces transfusion requirements in anemic cancer patients receiving chemotherapy.
Adolescent↗